DESCRIPTION: (adapted from applicant's description) Many compounds such as insecticides, plasticizers, and dioxins can be classified as environmental estrogens or endocrine disrupters. Exposure of women to these chemicals in the environment, in the food chain, and through occupational exposures, may affect women's health and, through increases in birth defects, the health of future generations. This proposal examines a panel of chemicals to determine their potential to affect women's health and the health of future offspring. These studies will examine the regulatory potential of these compounds in estrogenic and non-estrogenic pathways, and the biological mechanisms used by these compounds in gene regulation. The hypothesis that each compound affects estrogenic pathways will be tested. A novel assay will be used to determine binding to estrogen receptor. Gene regulation studies in tissue culture systems will be used to determine the capacity of these compounds to participate as agonists or antagonists in known mechanisms of estrogenic gene regulation. Differential display PCR will be used to determine if compounds can alter endogenous gene expression by estrogenic or non-estrogenic pathways. Finally, results from these in vitro studies will be confirmed in animals, using the recently created estrogen receptor "knock-out" mouse and normal litter mates.